Medical device related microbial infections pose serious clinical and economic costs. One mechanism for reducing these costs and potentially serious negative health outcomes, is to provide antimicrobial coatings on medical devices. Antimicrobial coatings for biomedical devices have been described. For example, coatings containing antibiotics, quaternary ammonium compounds, and silver have been described. However, use of these coatings, particularly on medical devices, has disadvantages. For instance, the use of antibiotic coatings may lead to the development of antibiotic resistant microorganisms and quaternary ammonium compounds often elicit irritancy. There exists a need for safe and effective antimicrobial surfaces applied to medical devices.
Moreover, there are many other products or articles in which an antimicrobial surface or coating would be beneficial. These include, in addition to medical devices, non-woven fabric, fiber, films and barrier materials such as wound dressings, surgical gowns, gloves, aprons, and drapes.
Antimicrobial peptides (AMPs) are ubiquitous in nature and play an important role in the innate immune system of many species (Zasloff, M., Nature (2002) 415:389-395; Epand, R. M., and Vogel, H. J., Biochim Biophys Acta (1999) 1462:11-28). Antimicrobial peptides are diverse in structure, function, and specificity. The structure of AMPs can be divided into two classes: linear peptides with no cysteine residues, and peptides with cysteine residues which contain one or multiple disulfide bonds. These structurally diverse AMPs share a common structural motif in that they are often cationic and amphiphilic. Amphiphilic peptides are characterized by spatially segregated polar and non-polar residues. It is believed that the cationic amphiphilic AMPs interact with the negatively charged bacterial cell membrane. The interaction of antimicrobial peptides with bacteria is thought to produce membrane perturbations, leading to rapid cell death (Shai, Y., Biochim Biophys Acta (1999) 1462:55-70; Matsuzaki, K., Biochim Biophys Acta (1999) 1462:1-10; Yang, et al. Biophys. J. (2000) 79:2002-2009). Due to the non-specific mode of action of antimicrobial peptides, resistance to the antimicrobial peptides is thought to be less likely than antibiotics that act on specific targets (Zasloff, supra; Epand, supra).
WO2002/064183 discloses biomedical devices with antimicrobial cationic peptide and protein coatings. In particular, contact lenses coated with protamine, melittin, cepropin A, nisin, or a combination thereof, exhibited antimicrobial properties. The coating process involved contacting the lens material with a solution of antimicrobial peptides.
WO2004/056402 discloses a coated biomedical device wherein the device contained a latent reactive component coated with a peptide containing coating.
WO2004/056407 discloses biomedical devices with antimicrobial coatings. In particular, contact lenses coated with L-melimine, protamine or combinations thereof, reduce by greater than about 50 percent, either or both, the number of bacteria adhering to the surface and the growth of bacteria adhering to the surface.
U.S. Pat. No. 5,847,047 describes compositions containing polymer-bound oligopeptides. According to this reference, cationic oligopeptides comprised of leucine and lysine residues exhibited antimicrobial activity when bound to polymeric materials.
Reaction of polyamides with formaldehyde is known. Lin et. al. described the reaction of nylon with aqueous formaldehyde under basic condition (Jian Lin, Catherine Winkelman, S. D. Worley, R. M. Broughton, J. E. Williams, J. Appl. Poly. Science, 81, 943-947 (2001). U.S. Pat. No. 4,182,695 discloses the bonding of biologically active proteins on polyamides by first reaction of polyamide with formaldehyde and a compound condensable with formaldehyde that contains at least one further reactive group, and reacting the product with a protein.
Functionalization of amides, lactams, and imides with formaldehyde, and further reaction of the hydroxymethyl intermediate under the action of hydrogen halide, thionyl chloride, or a phosphorous halide is known (H. E. Zaugg and W. B. Martin, Org. React., 14, 52 (1965)). An alternate procedure utilizing halosilanes in the synthesis of N-(halomethyl) derivatives of lactams, N-methylcarboxyamides, and imides is described by Orlova, N. A. et. al (N. A. Orlova, A. G. Shipov, I. A. Savost'yanova, Yu. I. Baukov, Russian Journal of general chemistry (English trans) EN: 61, 9.2; 1991; 1875-1881.)
Applicants have found processes for providing durable antimicrobial surfaces that include treating a polymer substrate with formaldehyde followed by treatment with an antimicrobial peptide.